Pyrrolo[2,3-d]pyrimidine compounds

ABSTRACT

A compound of the formula                    
     wherein R 1 , R 2  and R 3  are as defined above, useful as inhibitors of protein kinases, such as the enzyme Janus Kinase 3.

CROSS-REFERENCE TO RELATED APPLICATION

This non-provisional application is based upon and claims priority fromU.S. provisional patent application No. 60/214,287, filed Jun. 26, 2000.

BACKGROUND OF THE INVENTION

The present invention relates to pyrrolo[2,3-d]pyrimidine compoundswhich are inhibitors of protein kinases, such as the enzyme Janus Kinase3 (hereinafter also referred to as JAK3) and as such are useful therapyas immunosuppressive agents for organ transplants, xeno transplantation,lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type Idiabetes and complications from diabetes, cancer, asthma, atopicdermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn'sdisease, Alzheimer's disease, Leukemia and other indications whereimmunosuppression would be desirable.

This invention also relates to a method of using such compounds in thetreatment of the above indications in mammals, especially humans, andthe pharmaceutical compositions useful therefor.

JAK3 is a member of the Janus family of protein kinases. Although theother members of this family are expressed by essentially all tissues,JAK3 expression is limited to hematopoetic cells. This is consistentwith its essential role in signaling through the receptors for IL-2,IL-4, IL-7, IL-9 and IL-15 by non-covalent association of JAK3 with thegamma chain common to these multichain receptors. XSCID patientpopulations have been identified with severely reduced levels of JAK3protein or with genetic defects to the common gamma chain, suggestingthat immunosuppression should result from blocking signaling through theJAK3 pathway. Animal studies have suggested that JAK3 not only plays acritical role in B and T lymphocyte maturation, but that JAK3 isconstitutively required to maintain T cell function. Modulation ofimmune activity through this novel mechanism can prove useful in thetreatment of T cell proliferative disorders such as transplant rejectionand autoimmune diseases.

SUMMARY OF THE INVENTION

The present invention relates to a compound of the formula

or the pharmaceutically acceptable salt thereof; wherein

R¹ is a group of the formula

wherein y is 0, 1 or 2;

R⁴ is selected from the group consisting of hydrogen, (C₁-C₆)alkyl,(C₁-C₆)alkylsulfonyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl wherein the alkyl,alkenyl and alkynyl groups are optionally substituted by deuterium,hydroxy, amino, trifluoromethyl, (C₁-C₄)alkoxy, (C₁-C₆)acyloxy,(C₁-C₆)alkylamino, ((C₁-C₆)alkyl)₂amino, cyano, nitro, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl or (C₁-C₆)acylamino; or R⁴ is (C₃-C₁₀)cycloalkyl whereinthe cycloalkyl group is optionally substituted by deuterium, hydroxy,amino, trifluoromethyl, (C₁-C₆)acyloxy, (C₁-C₆)acylamino,(C₁-C₆)alkylamino, ((C₁-C₆)alkyl)₂amino, cyano, cyano(C₁-C₆)alkyl,trifluoromethyl(C₁-C₆)alkyl, nitro, nitro(C₁-C₆)alkyl or(C₁-C₆)acylamino;

R⁵ is (C₂-C₉)heterocycloalkyl wherein the heterocycloalkyl groups mustbe substituted by one to five groups consisting of carboxy, cyano,amino, deuterium, hydroxy, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo,(C₁-C₆)acyl, (C₁-C₆)alkylamino, amino(C₁-C₆)alkyl, (C₁-C₆)alkoxy-CO—NH,(C₁-C₆)alkylamino-CO—, (C₂-C₆)alkenyl, (C₂-C₆) alkynyl,(C₁-C₆)alkylamino, amino(C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl,(C₁-C₆)alkoxy(C₁-C₆)alkyl, (C₁-C₆)acyloxy(C₁-C₆)alkyl, nitro,cyano(C₁-C₆)alkyl, halo(C₁-C₆)alkyl, nitro(C₁-C₆)alkyl, trifluoromethyl,trifluoromethyl(C₁-C₆)alkyl, (C₁-C₆)acylamino,(C₁-C₆)acylamino(C₁-C₆)alkyl, (C₁-C₆)alkoxy(C₁-C₆)acylamino,amino(C₁-C₆)acyl, amino(C₁-C₆)acyl(C₁-C₆)alkyl,(C₁-C₆)alkylamino(C₁-C₆)acyl, ((C₁-C₆)alkyl)₂amino(C₁-C₆)acyl,R¹⁵R¹⁶N—CO—O—, R¹⁵R¹⁶N-CO-(C₁-C₆)alkyl, (C₁-C₆)alkyl-S(O)_(m),R¹⁵R¹⁶NS(O)_(m), R¹⁵R¹⁶NS(O)_(m) (C₁-C₆)alkyl, R¹⁵S(O)m R¹⁶N,R¹⁵S(O)mR¹⁶N(C₁-C₆)alkyl wherein m is 0, 1 or 2 and R¹⁵ and R¹⁵ are eachindependently selected from hydrogen or (C₁-C₆)alkyl; and a group of theformula

wherein a is 0, 1, 2, 3 or 4;

b, c, e, f and g are each independently 0 or 1;

d is 0, 1, 2, or 3;

X is S(O)_(n) wherein n is 0, 1 or 2; oxygen, carbonyl or —C(═N-cyano)-;

Y is S(O)_(n) wherein n is 0, 1 or 2; or carbonyl; and

Z is carbonyl, C(O)O—, C(O)NR— wherein R is hydrogen or (C₁-C₆)alkyl; orZ is S(O)_(n) wherein n is 0, 1 or 2;

R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹ are each independently selected from thegroup consisting of hydrogen or (C₁-C₆)alkyl optionally substituted bydeuterium, hydroxy, amino, trifluoromethyl, (C₁-C₆)acyloxy,(C₁-C₆)acylamino, (C₁-C₆)alkylamino, ((C₁-C₆)alkyl)₂amino, cyano,cyano(C₁-C₆)alkyl, trifluoromethyl(C₁-C₆)alkyl, nitro, nitro(C₁-C₆)alkylor (C₁-C₆)acylamino;

R¹² is (C₆-C₁₀)aryl, (C₂-C₉)heteroaryl, (C₃-C₁₀)cycloalkyl or(C₂-C₉)heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl andheterocycloalkyl groups are optionally substituted by one to four groupsconsisting of hydrogen, deuterium, amino, halo, oxo, hydroxy, nitro,carboxy, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₃-C₁₀)cycloalkyl,(C₁-C₆)alkyl-CO—NH—, (C₁-C₆)alkoxy-CO—NH—,(C₁-C₆)alkyl-CO—NH—(C₁-C₆)alkyl, (C₁-C₆)alkoxy-CO—NH—(C₁-C₆)alkyl,(C₁-C₆)alkoxy-CO—NH—(C₁-C₆)alkoxy, carboxy, carboxy(C₁-C₆)alkyl,carboxy(C₁-C₆)alkoxy, benzyloxycarbonyl(C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl(C₁-C₆)alkoxy, (C₆-C₁₀)aryl, amino,amino(C₁-C₆)alkyl, (C₁-C₆)alkoxycarbonylamino,(C₆-C₁₀)aryl(C₁-C₆)alkoxycarbonylamino, (C₁-C₆)alkylamino,((C₁-C₆)alkyl)₂amino, (C₁-C₆)alkylamino(C₁-C₆)alkyl,((C₁-C₆)alkyl)₂amino(C₁-C₆)alkyl, hydroxy, (C₁-C₆)alkoxy, carboxy,carboxy(C₁-C₆)alkyl, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkoxycarbonyl(C₁-C₆)alkyl, (C₁-C₆)alkoxy-CO—NH—,(C₁-C₆)alkyl-CO—NH—, cyano, (C₅-C₉)heterocycloalkyl, amino-CO—NH—,(C₁-C₆)alkylamino-CO—NH—, ((C₁-C₆)alkyl)₂amino-CO—NH—,(C₆-C₁₀)arylamino-CO—NH—, (C₅-C₉)heteroarylamino-CO—NH—,(C₁-C₆)alkylamino-CO—NH—(C₁-C₆)alkyl,((C₁-C₆)alkyl)₂amino-CO—NH—(C₁-C₆)alkyl,(C₆-C₁₀)arylamino-CO—NH—(C₁-C₆)alkyl,(C₅-C₉)heteroarylamino-CO—NH—(C₁-C₆)alkyl, (C₁-C₆)alkylcyano,(C₁-C₆)alkylcarboxy(C₁-C₆)alkoxy, (C₁-C₆)alkylcarboxy, sulfonylamino,aminosulfonyl, sulfonylamino(C₁-C₆)alkyl,sulfonylaminocarboxy(C₁-C₆)alkyl, (C₁-C₆)alkylsulfonyl,(C₁-C₆)alkylsulfonylamino, (C₁-C₆)alkylsulfonylamino(C₁-C₆)alkyl,(C₆-C₁₀)arylsulfonyl, (C₆-C₁₀)arylsulfonylamino,(C₆-C₁₀)arylsulfonylamino(C₁-C₆)alkyl, (C₁-C₆)alkylsulfonylamino,(C₁-C₆)alkylsulfonylamino(C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl,(C₃-C₁₀)cycloalkoxy, (C₁-C₆)alkylamino, ((C₁-C₆)alkyl)₂amino,(C₆-C₁₀)arylamino, (C₁-C₆)alkylthio, (C₆-C₁₀)arylthio,(C₁-C₆)alkylsulfinyl, (C₆-C₁₀)arylsulfinyl, (C₁-C₆)alkylsulfonyl,(C₆-C₁₀)arylsulfonyl, (C₁-C₆)acyl, (C₁-C₆)alkoxy-CO—NH—,(C₁-C₆)alkyamino-CO—, (C₅-C₉)heteroaryl, (C₂-C₉)heterocycloalkyl or(C₆-C₁₀)aryl wherein the heteroaryl, heterocycloalkyl and aryl groupswhich are optionally substituted on R¹² may be further substituted byone to three groups consisting of halo, (C₁-C₆)alkyl,(C₁-C₆)alkyl-CO—NH—, (C₁-C₆)alkoxy-CO—NH—,(C₁-C₆)alkyl-CO—NH—(C₁-C₆)alkyl, (C₁-C₆)alkoxy-CO—NH—(C₁-C₆)alkyl,(C₁-C₆)alkoxy-CO—NH—(C₁-C₆)alkoxy, carboxy, carboxy(C₁-C₆)alkyl,carboxy(C₁-C₆)alkoxy, benzyloxycarbonyl(C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl(C₁-C₆)alkoxy, (C₆-C₁₀)aryl, amino,amino(C₁-C₆)alkyl, (C₁-C₆)alkoxycarbonylamino,(C₆-C₁₀)aryl(C₁-C₆)alkoxycarbonylamino, (C₁-C₆)alkylamino,((C₁-C₆)alkyl)₂amino, (C₁-C₆)alkylamino(C₁-C₆)alkyl,((C₁-C₆)alkyl)₂amino(C₁-C₆)alkyl, hydroxy, (C₁-C₆)alkoxy, carboxy,carboxy(C₁-C₆)alkyl, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkoxycarbonyl(C₁-C₆)alkyl, (C₁-C₆)alkoxy-CO—NH—,(C₁-C₆)alkyl-CO—NH—, cyano, (C₅-C₉)heterocycloalkyl, amino-CO—NH—,(C₁-C₆)alkylamino-CO—NH—, ((C₁-C₆)alkyl)₂amino-CO—NH—,(C₆-C₁₀)arylamino-CO—NH—, (C₅-C₉)heteroarylamino-CO—NH—,(C₁-C₆)alkylamino-CO—NH—(C₁-C₆)alkyl,((C₁-C₆)alkyl)₂amino-CO—NH—(C₁-C₆)alkyl,(C₆-C₁₀)arylamino-CO—NH—(C₁-C₆)alkyl,(C₅-C₉)heteroarylamino-CO—NH—(C₁-C₆)alkyl, (C₁-C₆)alkylsulfonyl,(C₁-C₆)alkylsulfonylamino, (C₁-C₆)alkylsulfonylamino(C₁-C₆)alkyl,(C₆-C₁₀)arylsulfonyl, (C₆-C₁₀)arylsulfonylamino,(C₆-C₁₀)arylsulfonylamino(C₁-C₆)alkyl, (C₁-C₆)alkylsulfonylamino,(C₁-C₆)alkylsulfonylamino(C₁-C₆)alkyl, (C₅-C₉)heteroaryl and(C₂-C₉)heterocycloalkyl;

R² and R³ are each independently selected from the group consisting ofhydrogen, deuterium, amino, halo, hydroxy, nitro, carboxy,(C₂-C₆)alkenyl, (C₂-C₆)alkynyl, trifluoromethyl, trifluoromethoxy,(C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₃-C₁₀)cycloalkyl wherein the alkyl,alkoxy or cycloalkyl groups are optionally substittued by one to threegroups selected from halo, hydroxy, carboxy, amino (C₁-C₆)alkylthio,(C₁-C₆)alkylamino, ((C₁-C₆)alkyl)₂amino, (C₅-C₉)heteroaryl,(C₂-C₉)heterocycloalkyl, (C₃-C₉)cycloalkyl or (C₆-C₁₀)aryl; or R² and R³are each independently (C₃-C₁₀)cycloalkyl, (C₃-C₁₀)cycloalkoxy,(C₁-C₆)alkylamino, ((C₁-C₆)alkyl)₂amino, (C₆-C₁₀)arylamino,(C₁-C₆)alkylthio, (C₆-C₁₀)arylthio, (C₁-C₆)alkylsulfinyl,(C₆-C₁₀)arylsulfinyl, (C₁-C₆)alkylsulfonyl, (C₆-C₁₀)arylsulfonyl,(C₁-C₆)acyl, (C₁-C₆)alkoxy-CO—NH, (C₁-C₆)alkyamino-CO—,(C₅-C₉)heteroaryl, (C₂-C₉)heterocycloalkyl or (C₆-C₁₀)aryl wherein theheteroaryl, heterocycloalkyl and aryl groups are optionally substitutedby one to three halo, (C₁-C₆)alkyl, (C₁-C₆)alkyl-CO—NH—,(C₁-C₆)alkoxy-CO—NH—, (C₁-C₆)alkyl-CO—NH—(C₁-C₆)alkyl,(C₁-C₆)alkoxy-CO—NH—(C₁-C₆)alkyl, (C₁-C₆)alkoxy-CO—NH—(C₁-C₆)alkoxy,carboxy, carboxy(C₁-C₆)alkyl, carboxy(C₁-C₆)alkoxy,benzyloxycarbonyl(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl(C₁-C₆)alkoxy,(C₆-C₁₀)aryl, amino, amino(C₁-C₆)alkyl, (C₁-C₆)alkoxycarbonylamino,(C₆-C₁₀)aryl(C₁-C₆)alkoxycarbonylamino, (C₁-C₆)alkylamino,((C₁-C₆)alkyl)₂amino, (C₁-C₆)alkylamino(C₁-C₆)alkyl,((C₁-C₆)alkyl)₂amino(C₁-C₆)alkyl, hydroxy, (C₁-C₆)alkoxy, carboxy,carboxy(C₁-C₆)alkyl, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkoxycarbonyl(C₁-C₆)alkyl, (C₁-C₆)alkoxy-CO—NH—,(C₁-C₆)alkyl-CO—NH—, cyano, (C₅-C₉)heterocycloalkyl, amino-CO—NH—,(C₁-C₆)alkylamino-CO—NH—, ((C₁-C₆)alkyl)₂amino-CO—NH—,(C₆-C₁₀)arylamino-CO—NH—, (C₅-C₉)heteroarylamino-CO—NH—,(C₁-C₆)alkylamino-CO—NH—(C₁-C₆)alkyl,((C₁-C₆)alkyl)₂amino-CO—NH—(C₁-C₆)alkyl,(C₆-C₁₀)arylamino-CO—NH—(C₁-C₆)alkyl,(C₅-C₉)heteroarylamino-CO—NH—(C₁-C₆)alkyl, (C₁-C₆)alkylsulfonyl,(C₁-C₆)alkylsulfonylamino, (C₁-C₆)alkylsulfonylamino(C₁-C₆)alkyl,(C₆-C₁₀)arylsulfonyl, (C₆-C₁₀)arylsulfonylamino,(C₆-C₁₀)arylsulfonylamino(C₁-C₆)alkyl, (C₁-C₆)alkylsulfonylamino,(C₁-C₆)alkylsulfonylamino(C₁-C₆)alkyl, (C₅-Ca)heteroaryl or(C₂-C₉)heterocycloalkyl;

with the proviso that R⁵ must be substituted by the group of formula II.

The present invention also relates to the pharmaceutically acceptableacid addition salts of compounds of the formula I. The acids which areused to prepare the pharmaceutically acceptable acid addition salts ofthe aforementioned base compounds of this invention are those which formnon-toxic acid addition salts, i.e., salts containing pharmacologicallyacceptable anions, such as the hydrochloride, hydrobromide, hydroiodide,nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate,lactate, citrate, acid citrate, tartrate, bitartrate, succinate,maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate,ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [i.e.,1,1′-methylene-bis-(2-hydroxy-3-naphthoate)]salts.

The invention also relates to base addition salts of formula I. Thechemical bases that may be used as reagents to prepare pharmaceuticallyacceptable base salts of those compounds of formula I that are acidic innature are those that form non-toxic base salts with such compounds.Such non-toxic base salts include, but are not limited to those derivedfrom such pharmacologically acceptable cations such as alkali metalcations (e.g., potassium and sodium) and alkaline earth metal cations(e.g., calcium and magnesium), ammonium or water-soluble amine additionsalts such as N-methylglucamine-(meglumine), and the loweralkanolammonium and other base salts of pharmaceutically acceptableorganic amines.

The term “Oxone®” is a name of a monopersulfate compound used in thisinvention, having the formula 2KHSO₅.KHSO₄.K₂SO₄, and sold by AldrichChemical Company, P.O. Box 2060, Milwaukee, Wis. 53201, USA.

The term “alkyl”, as used herein, unless otherwise indicated, includessaturated monovalent hydrocarbon radicals having straight or branchedmoieties or combinations thereof.

The term “alkoxy”, as used herein, includes 0-alkyl groups wherein“alkyl” is defined above.

The term “halo”, as used herein, unless otherwise indicated, includesfluoro, chloro, bromo or iodo.

The compounds of this invention may contain double bonds. When suchbonds are present, the compounds of the invention exist as cis and transconfigurations and as mixtures thereof.

Unless otherwise indicated, the alkyl and alkenyl groups referred toherein, as well as the alkyl moieties of other groups referred to herein(e.g., alkoxy), may be linear or branched, and they may also be cyclic(e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl)or be linear or branched and contain cyclic moieties. Unless otherwiseindicated, halogen includes fluorine, chlorine, bromine, and iodine.

(C₂-C₉) Heterocycloalkyl when used herein refers to pyrrolidinyl,tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyranyl,thiopyranyl, aziridinyl, oxiranyl, methylenedioxyl, chromenyl,isoxazolidinyl, 1,3-oxazolidin-3-yl, isothiazolidinyl,1,3-thiazolidin-3-yl, 1,2-pyrazolidin-2-yl, 1,3-pyrazolidin-1-yl,piperidinyl, thiomorpholinyl, 1,2-tetrahydrothiazin-2-yl,1,3-tetrahydrothiazin-3-yl, tetrahydrothiadiazinyl, morpholinyl,1,2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl,tetrahydroazepinyl, piperazinyl, chromanyl, etc. One of ordinary skillin the art will understand that the connection of said (C₂-C₉)heterocycloalkyl rings is through a carbon or a sp³ hybridized nitrogenheteroatom.

(C₂-C₉) Heteroaryl when used herein refers to furyl, thienyl, thiazolyl,pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, triazolyl,tetrazolyl, imidazolyl, 1,3,5-oxadiazolyl, 1,2,4-oxadiazolyl,1,2,3-oxadiazolyl, 1,3,5-thiadiazolyl, 1,2,3-thiadiazolyl,1,2,4-thiadiazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl,1,2,4-triazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, pyrazolo[3,4-b]pyridinyl, cinnolinyl, pteridinyl, purinyl,6,7-dihydro-5H-[1]pyrindinyl, benzo[b]thiophenyl, 5, 6, 7,8-tetrahydro-quinolin-3-yl, benzoxazolyl, benzothiazolyl,benzisothiazolyl, benzisoxazolyl, benzimidazolyl, thianaphthenyl,isothianaphthenyl, benzofuranyl, isobenzofuranyl, isoindolyl, indolyl,indolizinyl, indazolyl, isoquinolyl, quinolyl, phthalazinyl,quinoxalinyl, quinazolinyl, benzoxazinyl etc. One of ordinary skill inthe art will understand that the connection of said (C₂-C₉)heteroarylrings is through a carbon atom or a sp³ hybridized nitrogen heteroatom.

(C₆-C₁₀)aryl when used herein refers to phenyl or naphthyl.

Compounds of formula (I) may be administered in a pharmaceuticallyacceptable form either alone or in combination with one or moreadditional agents which modulate a mammalian immune system or withantiinflammatory agents. These agents may include but are not limited tocyclosporin A (e.g. Sandimmune® or Neoral®, rapamycin, FK-506(tacrolimus), leflunomide, deoxyspergualin, mycophenolate (e.g.Cellcept®), azathioprine (e.g. Imuran®), daclizumab (e.g. Zenapax®. OKT3(e.g. Orthoclone®), AtGam, aspirin, acetaminophen, ibuprofen, naproxen,piroxicam, and antiinflammatory steroids (e.g. prednisolone ordexamethasone). These agents may be administered as part of the same orseparate dosage forms, via the same or different routes ofadministration, and on the same or different administration schedulesaccording to standard pharmaceutical practice.

The compounds of this invention include all conformational isomers(e.g., cis and trans isomers. The compounds of the present inventionhave asymmetric centers and therefore exist in different enantiomericand diastereomeric forms. This invention relates to the use of alloptical isomers and stereoisomers of the compounds of the presentinvention, and mixtures thereof, and to all pharmaceutical compositionsand methods of treatment that may employ or contain them. In thisregard, the invention includes both the E and Z configurations. Thecompounds of formula I may also exist as tautomers. This inventionrelates to the use of all such tautomers and mixtures thereof.

This invention also encompasses pharmaceutical compositions containingprodrugs of compounds of the formula I. This invention also encompassesmethods of treating or preventing disorders that can be treated orprevented by the inhibition of protein kinases, such as the enzyme JanusKinase 3 comprising administering prodrugs of compounds of the formulaI. Compounds of formula I having free amino, amido, hydroxy orcarboxylic groups can be converted into prodrugs. Prodrugs includecompounds wherein an amino acid residue, or a polypeptide chain of twoor more (e.g., two, three or four) amino acid residues which arecovalently joined through peptide bonds to free amino, hydroxy orcarboxylic acid groups of compounds of formula I. The amino acidresidues include the 20 naturally occurring amino acids commonlydesignated by three letter symbols and also include, 4-hydroxyproline,hydroxylysine, demosine, isodemosine, 3-methylhistidine, norvlin,beta-alanine, gamma-aminobutyric acid, citrulline, homocysteine,homoserine, ornithine and methioine sulfone. Prodrugs also includecompounds wherein carbonates, carbamates, amides and alkyl esters whichare covalently bonded to the above substituents of formula I through thecarbonyl carbon prodrug sidechain.

Preferred compounds of formula I include those wherein R⁵ is(C₂-C₉)heterocycloalkyl optionally substituted by one to three groupsselected from deuterium, hydroxy, (C₁-C₆)alkyl, halo, (C₁-C₆)alkoxy anda group of formula II.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is carbonyl; c is 0; d is 0; e is 0; f is 0; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is carbonyl; c is 0; d is 1; e is 0; f is 0, and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is carbonyl; c is 1; d is 0; e is 0; f is 0; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is —C(=cyano)-; c is 1; d is 0; e is 0; f is 0; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 0; c is 0; d is 0; e is 0; f is 0; g is 1; and Z is —C(O)—O—.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is S(O)_(n); n is 2; c is 0; d is 0; e is 0; f is 0; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is S(O)_(n); n is 2; c is 0; d is 2; e is 0; f is 1; g is 1; andZ is carbonyl.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is S(O)_(n); n is 2; c is 0; d is 2; e is 0; f is 1; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is carbonyl; c is 1; d is 0; e is 1; Y is S(O)_(n); n is 2; f is0; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is S(O)_(n); n is 2; c is 1; d is 0; e is 0; f is 0; and g is 0.

Other preferred compounds of formula I include those wherein a is 1; bis 1; X is carbonyl; c is 1; d is 0; e is 0; f is 0; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is S(O)_(n); c is 0; d is 1; e is 1; Y is S(O)_(n); n is 2; f is0; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is S(O)_(n); c is 0; d is 1; e is 1; Y is S(O)_(n); n is 2; f is1; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is oxygen; c is 0; d is 1; e is 1; Y is S(O)_(n); n is 2; f is1; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is oxygen; c is 0; d is 1; e is 1; Y is S(O)_(n); n is 2; f is0; and g is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is carbonyl; c is 1; d is 1; e is 1; Y is S(O)_(n); f is 0; andg is 0.

Other preferred compounds of formula I include those wherein a is 0; bis 1; X is carbonyl; c is 1; d is 1; e is 1; Y is S(O)_(n); n is 2; f is1; and g is 0.

Other preferred compounds of formula I include those wherein R¹² is(C₆-C₁₀)aryl or (C₂-C₉)heteroaryl wherein the aryl or heteroaryl groupis optionally substituted by one to four groups consisting of hydrogen,halo, hydroxy, carboxy, trifluormethyl, (C₁-C₆)alkyl, (C₁-C₀ ₆)alkoxy,(C₁-C₆)alkyl-CO—NH—, amino, amino(C₁-C₆)alkyl, (C₁-C₆)alkylamino,((C₁-C₆)alkyl)₂amino, cyano, amino-CO—NH—, (C₁-C₆)alkylamino-CO—NH—,((C₁-Cc₆)alkyl)₂amino-CO—NH—, (C₅-C₉)heteroarylamino-CO—NH—,(C₁-C₆)alkylsulfonyl, (C₁-C₆)alkylsulfonylamino,(C₆-C₁₀)arylsulfonylamino, (C₁-C₆)alkylsulfonylamino, and(C₁-C₆)alkoxy-CO—NH—.

Specific preferred compounds of formula I include those wherein saidcompound is selected from the group consisting of:

4-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzenesulfonamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-sulfamoyl-phenyl)-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-nitro-phenyl)-amide;

-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-tetrazol-1-yl-ethanone;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-methylsulfamoyl-phenyl)-amide;

(3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone;

[2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-yl]-aceticacid;

Methyl-(4-methyl-5′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine;

5-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-thiazolidine-2,4-dione;

{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-thiazolidin-3-yl-methanone;

Methyl-[4-methyl-1-(5-nitro-thiazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine;

[2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-yl]-aceticacid ethyl ester;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid thiazol-2-ylamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-cyano-phenyl)-amide;

{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-pyrrolidin-1-yl-methanone;

Furan-2-carboxylic acid(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide;

{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}(tetrahydro-furan-3-yl)-methanone;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid isoxazol-3-ylamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (6-cyano-pyridin-3-yl)-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carbonitrile

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-methyl-thiazol-2-yl)-amide;

2-Cyclopropyl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone;

Cyclopentyl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-Methanone;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (3-methyl-isoxazol-4-yl)-amide;

[4-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-phenyl]-aceticacid;

[1-(5-Amino-thiazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (3-methyl-isothiazol-5-yl)-amide;

3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-cyclopentanone;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid benzyl-methyl-amide; and

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid dimethylamide.

The present invention also relates to a pharmaceutical composition for(a) treating or preventing a disorder or condition selected from organtransplant rejection, xeno transplantation, lupus, multiple sclerosis,rheumatoid arthritis, psoriasis, Type I diabetes and complications fromdiabetes, cancer, asthma, atopic dermatitis, autoimmune thyroiddisorders, ulcerative colitis, Crohn's disease, Alzheimer's disease,Leukemia, and other autoimmune diseases or (b) the inhibition of proteinkinases or Janus Kinase 3 (JAK3) in a mammal, including a human,comprising an amount of a compound of formula I or a pharmaceuticallyacceptable salt thereof, effective in such disorders or conditions and apharmaceutically acceptable carrier.

The present invention also relates to a method for the inhibition ofprotein typrosine kinases or Janus Kinase 3 (JAK3) in a mammal,including a human, comprising administering to said mammal an effectiveamount of a compound of formula I or a pharmaceutically acceptable saltthereof.

The present invention also relates to a method for treating orpreventing a disorder or condition selected from organ transplantrejection, xeno transplantation, lupus, multiple sclerosis, rheumatoidarthritis, psoriasis, Type I diabetes and complications from diabetes,cancer, asthma, atopic dermatitis, autoimmune thyroid disorders,ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, andother autoimmune diseases in a mammal, including a human, comprisingadministering to said mammal an amount of a compound of formula I or apharmaceutically acceptable salt thereof, effective in treating such acondition.

DETAILED DESCRIPTION OF THE INVENTION

The following reaction Schemes illustrate the preparation of thecompounds of the present invention. Unless otherwise indicated R², R³,R⁴ and R⁵ in the reaction Schemes and the discussion that follow aredefined as above.

In reaction 1 of Preparation A, the 4-chloropyrrolo[2,3-d]pyrimidinecompound of formula XXI, wherein R is hydrogen or a protecting groupsuch as benzenesulfonyl or benzyl, is converted to the4-chloro-5-halopyrrolo[2,3-d]pyrimidine compound of formula XX, whereinY is chloro, bromo or iodo, by reacting XXI with N-chlorosuccinimide,N-bromosuccinimide or N-iodosuccinimide. The reaction mixture is heatedto reflux, in chloroform, for a time period between about 1 hour toabout 3 hours, preferably about 1 hour. Alternatively, in reaction 1 ofPreparation A, the 4-chloropyrrolo[2,3-d]pyrimidine of formula XXI,wherein R is hydrogen, is converted to the corresponding4-chloro-5-nitropyrrolo[2,3-d]pyrimidine of formula XX, wherein Y isnitro, by reacting XXI with nitric acid in sulfuric acid at atemperature between about −10° C. to about 10° C., preferably about 0°C., for a time period between about 5 minutes to about 15 minutes,preferably about 10 minutes. The compound of formula XXI, wherein Y isnitro, is converted to the corresponding4-chloro-5-aminopyrrolo[2,3-d]pyrimidine of the formula XX, wherein Y isamino, by reacting XXI under a variety of conditions known to oneskilled in the art such as palladium hydrogenolysis or tin(IV)chlorideand hydrochloric acid.

In reaction 2 of Preparation A, the4-chloro-5-halopyrrolo[2,3-d]pyrimidine compound of formula XX, whereinR is hydrogen, is converted to the corresponding compound of formulaXIX, wherein R² is (C₁-C₆)alkyl or benzyl, by treating XX withN-butyllithium, at a temperature of about −78° C., and reacting thedianion intermediate so formed with an alkylhalide or benzylhalide at atemperature between about −78° C. to room temperature, preferably roomtemperature. Alternatively, the dianion so formed is reacted withmolecular oxygen to form the corresponding4-chloro-5-hydroxypyrrolo[2,3-d]pyrimidine compound of formula XIX,wherein R² is hydroxy. The compound of formula XX, wherein Y is bromineor iodine and R is benzenesulfonate, is converted to the compound offormula XIX, wherein R² is (C₆-C₁₂)aryl or vinyl, by treating XX withN-butyllithium, at a temperature of about −78° C., followed by theaddition of zinc chloride, at a temperature of about −78° C. Thecorresponding organo zinc intermediate so formed is then reacted witharyliodide or vinyl iodide in the presence of a catalytic quantity ofpalladium. The reaction mixture is stirred at a temperature betweenabout 50° C. to about 80° C., preferably about 70° C., for a time periodbetween about 1 hour to about 3 hours, preferably about 1 hour.

In reaction 3 of Preparation A, the compound of formula XIX is convertedto the corresponding compound of formula XVI by treating XIX withN-butyllithium, lithium diisopropylamine or sodium hydride, at atemperature of about −78° C., in the presence of a polar aproticsolvent, such as tetrahydrofuran. The anionic intermediate so formed isfurther reacted with (a) alkylhalide or benzylhalide, at a temperaturebetween about −78° C. to room temperature, preferably −78° C., when R³is alkyl or benzyl; (b) an aldehyde or ketone, at a temperature betweenabout −78° C. to room temperature, preferably −78° C., when R³ isalkoxy; and (c) zinc chloride, at a temperature between about −78° C. toroom temperature, preferably −78° C., and the corresponding organozincintermediate so formed is then reacted with aryliodide or vinyl iodidein the presence of a catalytic quantity of palladium. The resultingreaction mixture is stirred at a temperature between about 50° C. toabout 80° C., preferably about 70° C., for a time period between about 1hour to about 3 hours, preferably about 1 hour. Alternatively, the anionso formed is reacted with molecular oxygen to form the corresponding4-chloro-6-hydroxypyrrolo[2,3-d]pyrimidine compound of formula XVI,wherein R³ is hydroxy.

In reaction 1 of Preparation B, the 4-chloropyrrolo[2,3-d]pyrimidinecompound of formula XXI is converted to the corresponding compound offormula XXII, according to a procedure analogous to that described abovein reaction 3 of Preparation A.

In reaction 2 of Preparation B, the compound of formula XXII isconverted to the corresponding compound of formula XVI, according toprocedures analogous to that described above in reactions 1 and 2 ofPreparation A.

In reaction 1 of Preparation C, the 4-methylpyridine compound of formulaXXXI is converted to the corresponding compound of formula XXX by firstalkylating XXXI with benzylchloride in the presence of a polar aproticsolvent, such as acetone. The reaction mixture is stirred at atemperature between about 40° C. to about 80° C. for a time periodbetween about 4 hours to about 24 hours. The pyridinium intermediate soformed is then reduced with a reducing agent, such as sodiumborohydride, in the presence of a polar protic solvent, such asmethanol, ethanol, water or mixtures thereof. The reaction is stirred ata temperature between about 0° C. to a about room temperature, for atime period between about 18 hours to 24 hours.

In reaction 2 of Preparation C, the compound of formula XXX is convertedto the corresponding compound of formula XXIX by treating XXX withborotrifluoride etherate in the presence of a reducing agent and anaprotic solvent, such as tetrahydrofuran. The reaction mixture isstirred at a temperature between about 0° C. to room temperature, for atime period between about 1 hour to about 3 hours. The intermediatecomplex so formed is then basified with aqueous sodium hydroxide andthen treated with an oxidizing agent, such as hydrogen peroxide orOxone®, at a temperature between about 0° C. to room temperature, for atime period between about 12 hours to about 24 hours.

In reaction 3 of Preparation C, the compound of formula XXIX is treatedwith an oxidizing agent, such as chromium oxide or dimethylsulfoxide,oxalylchloride or SO₃-pyridine complex, for a time period between about1 hour to 3 hours, at ambient temperature. The ketone intermediate soformed, is then treated with an amine (R⁴-NH₂) in the presence of anacid, such as acetic acid, at about room temperature, for a time periodbetween about 2 to about 24 hours, in an organic solvent such asmethanol, ethanol or tetrahydrofuran. The corresponding imineintermediate so formed is then treated with a reducing agent, such assodium borohydride or sodium cyanoborohydride or sodiumtriacetoxyborohydride, at ambient temperature, for a time period about 2to about 24 hours.

In reaction 1 of Scheme 1, the 4-chloropyrrolo[2,3-d]pyrimidine compoundof formula XVII is converted to the corresponding compound of formulaXVI, wherein R is benzenesulfonyl or benzyl, by treating XVII withbenzenesulfonyl chloride, benzylchloride or benzylbromide in thepresence of a base, such as sodium hydride or potassium carbonate, and apolar aprotic solvent, such as dimethylformamide or tetrahydrofuran. Thereaction mixture is stirred at a temperature between about 0° C. toabout 70° C., preferably about 30° C., for a time period between about 1hour to about 3 hours, preferably about 2 hours.

In reaction 2 of Scheme 1, the 4-chloropyrrolo[2,3-d]pyrimidine compoundof formula XVI is converted to the corresponding4-aminopyrrolo[2,3-d]pyrimidine compound of formula XV by coupling XVIwith an amine of the formula HNR⁴R⁵. The reaction is carried out in analcohol solvent, such as tert-butanol, methanol or ethanol, or otherhigh boiling organic solvents, such as dimethylformamide, triethylamine,1,4-dioxane or 1,2-dichloroethane, at a temperature between about 60° C.to about 120° C., preferably about 80° C. Typical reaction times arebetween about 2 hours to about 48 hours, preferably about 16 hours. WhenR⁵ is a nitrogen containing heterocycloalkyl group, each nitrogen mustbe protected by a protecting group, such a benzyl. Removal of the R⁵protecting group is carried out under conditions appropriate for thatparticular protecting group in use which will not affect the Rprotecting group on the pyrrolo[2,3-d]pyrimidine ring. Removal of the R⁵protecting group, when benzyl, is carried out in an alcohol solvent,such as ethanol, in the present of hydrogen and a catalyst, such aspalladium hydroxide on carbon. The R⁵ nitrogen containinghetrocycloalkyl group so formed may be further reacted with a variety ofdifferent electrophiles of formula II. For urea formation, electrophilesof formula II such as isocyanates, carbamates and carbamoyl chloridesare reacted with the R⁵ nitrogen of the heteroalkyl group in a solvent,such as acetonitrile or dimethylformamide, in the presence of a base,such as sodium or potassium carbonate, at a temperature between about20° C. to about 100° C. for a time period between about 24 hours toabout 72 hours. For amide and sulfonamide formation, electrophiles offormula II, such as acylchlorides and sulfonyl chlorides, are reactedwith the R⁵ nitrogen of the heteroalkyl group in a solvent such asmethylene chloride in the presence of a base such as pyridine at ambienttemperatures for a time period between about 12 hours to about 24 hours.Amide formation may also be carried out by reacting a carboxylic acidwith the heteroalkyl group in the presence of a carbodiimide such as1-(3-dimethylaminopropyl)-3-ethylcarbodiimide in a solvent such asmethylene chloride at ambient temperatures for 12-24 hours. For alkylformation, electrophiles of formula II, such as α,β-unsaturated amides,acids, nitriles, esters, and a-halo amides, are reacted with the R⁵nitrogen of the heteroalkyl group in a solvent such as methanol atambient temperatures for a time period between about 12 hours to about18 hours. Alkyl formation may also be carried out by reacting aldehydeswith the heteroalkyl group in the presence of a reducing agent, such assodium cyanoborohydride, in a solvent, such as methanol, at ambienttemperature for a time period between about 12 hours to about 18 hours.

In reaction 3 of Scheme 1, removal of the protecting group from thecompound of formula XV, wherein R is benzenesulfonyl, to give thecorresponding compound of formula 1, is carried out by treating XV withan alkali base, such as sodium hydroxide or potassium hydroxide, in analcohol solvent, such as methanol or ethanol, or mixed solvents, such asalcohol/tetrahydrofuran or alcohol/water. The reaction is carried out atroom temperature for a time period between about 15 minutes to about 1hour, preferably 30 minutes. Removal of the protecting group from thecompound of formula XV, wherein R is benzyl, is conducted by treating XVwith sodium in ammonia at a temperature of about −78° C. for a timeperiod between about 15 minutes to about 1 hour.

In reaction 1 of Scheme 2, the 4-chloropyrrolo[2,3-d]pyrimidine compoundof formula XX is converted to the corresponding4-aminopyrrolo[2,3-d]pyrimidine compound of formula XXIV, according to aprocedure analogous to that described above in reaction 2 of Scheme 1.

In reaction 2 of Scheme 2, the 4-amino-5-halopyrrolo[2,3-d]pyrimidinecompound of formula XXIV, wherein R is benzenesulfonate and Z is bromineor iodine, is converted to the corresponding compound of formula XXIIIby reacting XXIV with (a) arylboronic acid, when R² is aryl, in anaprotic solvent, such tetrahydrofuran or dioxane, in the presence of acatalytic quantity of palladium (0) at a temperature between about 50°C. to about 100° C., preferably about 70° C., for a time period betweenabout 2 hours to about 48 hours, preferably about 12 hours; (b) 2alkynes, when R is alkynyl, in the presence of a catalytic quantity ofcopper (I) iodide and palladium (0), and a polar solvent, such asdimethylformamide, at room temperature, for a time period between about1 hour to about 5 hours, preferably about 3 hours; and (c) alkenes orstyrenes, when R² is vinyl or styrenyl, in the presence of a catalyticquantity of palladium in dimethylformamide, dioxane or tetrahydrofuran,at a temperature between about 80° C. to about 100° C., preferably about100° C., for a time period between about 2 hours to about 48 hours,preferably about 48 hours.

In reaction 3 of Scheme 2, the compound of formula XXIII is converted tothe corresponding compound of formula XV, according to a procedureanalogous to that described above in reaction 3 of Preparation A.

In reaction 1 of Scheme 3, the compound of formula XVII is converted tothe corresponding compound of formula 1, according to a procedureanalogous to that described above in reaction 2 of Scheme 1.

The compounds of the present invention that are basic in nature arecapable of forming a wide variety of different salts with variousinorganic and organic acids. Although such salts must bepharmaceutically acceptable for administration to animals, it is oftendesirable in practice to initially isolate the compound of the presentinvention from the reaction mixture as a pharmaceutically unacceptablesalt and then simply convert the latter back to the free base compoundby treatment with an alkaline reagent and subsequently convert thelatter free base to a pharmaceutically acceptable acid addition salt.The acid addition salts of the base compounds of this invention arereadily prepared by treating the base compound with a substantiallyequivalent amount of the chosen mineral or organic acid in an aqueoussolvent medium or in a suitable organic solvent, such as methanol orethanol. Upon careful evaporation of the solvent, the desired solid saltis readily obtained. The desired acid salt can also be precipitated froma solution of the free base in an organic solvent by adding to thesolution an appropriate mineral or organic acid.

Those compounds of the present invention that are acidic in nature, arecapable of forming base salts with various pharmacologically acceptablecations. Examples of such salts include the alkali metal oralkaline-earth metal salts and particularly, the sodium and potassiumsalts. These salts are all prepared by conventional techniques. Thechemical bases which are used as reagents to prepare thepharmaceutically acceptable base salts of this invention are those whichform non-toxic base salts with the acidic compounds of the presentinvention. Such non-toxic base salts include those derived from suchpharmacologically acceptable cations as sodium, potassium calcium andmagnesium, etc. These salts can easily be prepared by treating thecorresponding acidic compounds with an aqueous solution containing thedesired pharmacologically acceptable cations, and then evaporating theresulting solution to dryness, preferably under reduced pressure.Alternatively, they may also be prepared by mixing lower alkanolicsolutions of the acidic compounds and the desired alkali metal alkoxidetogether, and then evaporating the resulting solution to dryness in thesame manner as before. In either case, stoichiometric quantities ofreagents are preferably employed in order to ensure completeness ofreaction and maximum yields of the desired final product.

The compositions of the present invention may be formulated in aconventional manner using one or more pharmaceutically acceptablecarriers. Thus, the active compounds of the invention may be formulatedfor oral, buccal, intranasal, parenteral (e.g., intravenous,intramuscular or subcutaneous) or rectal administration or in a formsuitable for administration by inhalation or insufflation. The activecompounds of the invention may also be formulated for sustaineddelivery.

For oral administration, the pharmaceutical compositions may take theform of, for example, tablets or capsules prepared by conventional meanswith pharmaceutically acceptable excipients such as binding agents(e.g., pregelatinized maize starch, polyvinylpyrrolidone orhydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystallinecellulose or calcium phosphate); lubricants (e.g., magnesium stearate,talc or silica); disintegrants (e.g., potato starch or sodium starchglycolate); or wetting agents (e.g., sodium lauryl sulphate). Thetablets may be coated by methods well known in the art. Liquidpreparations for oral administration may take the form of, for example,solutions, syrups or suspensions, or they may be presented as a dryproduct for constitution with water or other suitable vehicle beforeuse. Such liquid preparations may be prepared by conventional means withpharmaceutically acceptable additives such as suspending agents (e.g.,sorbitol syrup, methyl cellulose or hydrogenated edible fats);emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles(e.g., almond oil, oily esters or ethyl alcohol); and preservatives(e.g., methyl or propyl p-hydroxybenzoates or sorbic acid).

For buccal administration, the composition may take the form of tabletsor lozenges formulated in conventional manner.

The active compounds of the invention may be formulated for parenteraladministration by injection, including using conventionalcatheterization techniques or infusion. Formulations for injection maybe presented in unit dosage form, e.g., in ampules or in multi-dosecontainers, with an added preservative. The compositions may take suchforms as suspensions, solutions or emulsions in oily or aqueousvehicles, and may contain formulating agents such as suspending,stabilizing and/or dispersing agents. Alternatively, the activeingredient may be in powder form for reconstitution with a suitablevehicle, e.g., sterile pyrogen-free water, before use.

The active compounds of the invention may also be formulated in rectalcompositions such as suppositories or retention enemas, e.g., containingconventional suppository bases such as cocoa butter or other glycerides.

For intranasal administration or administration by inhalation, theactive compounds of the invention are conveniently delivered in the formof a solution or suspension from a pump spray container that is squeezedor pumped by the patient or as an aerosol spray presentation from apressurized container or a nebulizer, with the use of a suitablepropellant, e.g., dichlorodifluoromethane, trichlorofluoromethane,dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In thecase of a pressurized aerosol, the dosage unit may be determined byproviding a valve to deliver a metered amount. The pressurized containeror nebulizer may contain a solution or suspension of the activecompound. Capsules and cartridges (made, for example, from gelatin) foruse in an inhaler or insufflator may be formulated containing a powdermix of a compound of the invention and a suitable powder base such aslactose or starch.

A proposed dose of the active compounds of the invention for oral,parenteral or buccal administration to the average adult human for thetreatment of the conditions referred to above (e.g., rheumatoidarthritis) is 0.1 to 1000 mg of the active ingredient per unit dosewhich could be administered, for example, 1 to 4 times per day.

Aerosol formulations for treatment of the conditions referred to above(e.g., asthma) in the average adult human are preferably arranged sothat each metered dose or “puff” of aerosol contains 20 μg to 1000 μg ofthe compound of the invention. The overall daily dose with an aerosolwill be within the range 0.1 mg to 1000 mg. Administration may beseveral times daily, for example 2, 3, 4 or 8 times, giving for example,1, 2 or 3 doses each time.

A compound of formula (I) administered in a pharmaceutically acceptableform either alone or in combination with one or more additional agentswhich modulate a mammlian immune system or with antiinflammatory agents,agents which may include but are not limited to cyclosporin A (e.g.Sandimmune® or Neoral®, rapamycin, FK-506 (tacrolimus), leflunomide,deoxyspergualin, mycophenolate (e.g. Cellcept®, azathioprine (e.g.Imuran®), daclizumab (e.g. Zenapax®), OKT3 (e.g. Orthocolone®), AtGam,aspirin, acctaminophen, ibuprofen, naproxen, piroxicam, andantiinflmmatory steroids (e.g. prednisolone or dexamethasone); and suchagents may be administered as part of the same or separate dosage forms,via the same or different routes of administration, and on the same ordifferent administration schedules according to standard pharmaceuticalpractice.

FK506 (Tacrolimus) is given orally at 0.10-0.15 mg/kg body weight, every12 hours, within first 48 hours postoperative. Does is monitored byserum Tacrolimus trough levels.

Cyclosporin A (Sandimmune oral or intravenous formulation, or Neoral®,oral solution or capsules) is given orally at 5 mg/kg body weight, every12 hours within 48 hours postoperative. Dose is monitored by bloodCyclosporin A trough levels.

The active agents can be formulated for sustained delivery according tomethods well known to those of ordinary skill in the art. Examples ofsuch formulations can be found in U.S. Pat. Nos. 3,538,214, 4,060,598,4,173,626, 3,119,742, and 3,492,397.

The ability of the compounds of formula I or their pharmaceuticallyacceptable salts to inhibit Janus Kinase 3 and, consequently,demonstrate their effectiveness for treating disorders or conditionscharacterized by Janus Kinase 3 is shown by the following in vitro assaytests.

Biological Assay

JAK3 (JH1:GST) Enzymatic Assay

The JAK3 kinase assay utilizes a protein expressed inbaculovirus-infected SF9 cells (a fusion protein of GST and thecatalytic domain of human JAK3) purified by affinity chromatography onglutathione-Sepaharose. The substrate for the reaction is poly-Glutamicacid-Tyrosine (PGT (4:1), Sigma catalog # P0275), coated onto Nunc MaxiSorp plates at 100 μg/ml overnight at 37° C. The morning after coating,the plates are washed three times and JAK3 is added to the wellscontaining 100 μl of kinase buffer (50 mM HEPES, pH 7.3,125 mM NaCl, 24mM MgCl2)+0.2 uM ATP+1 mM Na orthovanadate.) The reaction proceeds for30 minutes at room temperature and the plates is washed three moretimes. The level of phosphorylated tyrosine in a given well isquantitated by standard ELISA assay utilizing an anti-phosphotyrosineantibody (ICN PY20, cat. #69-151-1).

Inhibition of Human IL-2 Dependent T-Cell Blast Proliferation

This screen measures the inhibitory effect of compounds on IL-2dependent T-Cell blast proliferation in vitro. Since signaling throughthe IL-2 receptor requires JAK-3, cell active inhibitors of JAK-3 shouldinhibit IL-2 dependent T-Cell blast proliferation.

The cells for this assay are isolated from fresh human blood. Afterseparation of the mononuclear cells using AccuspinSystem-Histopaque-1077 (Sigma # A7054), primary human T-Cells areisolated by negative selection using Lympho-Kwik T (One Lambda, Inc.,Cat # LK-50T). T-Cells are cultured at 1-2×10⁶/ml in Media (RPMI+10%heat-inactivated fetal calf serum (Hyclone Cat # A-1111-L)+1%Penicillin/Streptomycin (Gibco)) and induce to proliferate by theaddition of 10 ug/ml PHA (Murex Diagnostics, Cat # HA 16). After 3 daysat 37° C. in 5% CO₂, cells are washed 3 times in Media, resuspended to adensity of 1-2×10⁶ cells/ml in Media plus 100 Units/ml of humanrecombinant IL-2 (R&D Systems, Cat # 202-IL). After 1 week the cells areIL-2 dependent and can be maintained for up to 3 weeks by feeding twiceweekly with equal volumes of Media+100 Units/ml of IL-2.

To assay for a test compounds ability to inhibit IL-2 dependent T-Cellproliferation, IL-2 dependent cells are washed 3 times, resuspended inmedia and then plated (50,000 cells/well/0.1 ml) in a Flat-bottom96-well microtiter plate (Falcon # 353075). From a 10 mM stock of testcompound in DMSO, serial 2-fold dilutions of compound are added intriplicate wells starting at 10 uM. After one hour, 10 Units/ml of IL-2is added to each test well. Plates are then incubated at 37° C., 5% CO₂for 72 hours. Plates are then pulsed with ³H-thymidine (0.5 uCi/well)(NEN Cat # NET -027A), and incubated an additional 18 hours. Cultureplates are then harvested with a 96-well plate harvester and the amountof ³H-thymidine incorporated into proliferating cells is determined bycounting on a Packard Top Count scintillation counter. Data is analyzedby plotting the % inhibition of proliferation verses the concentrationof test compound. An 1C50 value (uM) is determined from this plot.

The following Examples illustrate the preparation of the compounds ofthe present invention but it is not limited to the details thereof.Commercial reagents were utilized without further purification. THFrefers to tetrahydrofuran. DMF refers to N,N-dimethylformamide. LowResolution Mass Spectra (LRMS) were recorded on either a Hewlett Packard5989(, utilizing chemical ionization (ammonium), or a Fisons (or MicroMass) Atmospheric Pressure Chemical Ionization (APCI) platform whichuses a 50/50 mixture of acetonitrileiwater with 0.1% formic acid as theionizing agent. Room or ambient temperature refers to 20-25° C.

EXAMPLE 1Furan-2-yl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

Method A

1-Benzyl-4-methyl-pyridinium Chloride

To a stirred solution of 4-methylpyridine (26 mL/0.268 mol) in 70 mL ofacetone was added 31 mL (0.268 mol) of benzylchloride. The resultingmixture was stirred at 50° C. for 18 hours. After cooling to roomtemperature, the reaction was filtered, washed with acetone and driedunder reduced pressure affording 38 g of the title compound. Thefiltrate was concentrated under reduced pressure producing an additional5.6 grams of the title compound (74% combined yield).

LRMS: 184.

Method B

1-Benzyl-4-methyl-1,2,3,6-tetrahydro-pyridine

To a stirred solution of the product from Method A (38 grams/0.171 mol)dissolved in 140 mL of 10:1 ethanol/water at 0° C. was added 16 grams(0.427 mol) of sodium borohydride portion-wise over 25 minutes. Theresulting mixture stirred for 18 hours at room temperature, at whichtime, the reaction was quenched upon addition of 100 mL of water. Thereaction mixture was filtered, the filter cake washed with water andethylacetate, and the combined filtrates concentrated under reducedpressure to remove the organics. The residue was diluted with water (100mL) and extracted 3 times with 150 mL with ethylacetate. The combinedethylacetate extracts were dried over Na₂SO₄ and concentrated to drynessin vacuo affording 32 grams (100%) of the title compound as a yellowoil. LRMS: 188 (M+1).

Method C

1-Benzyl-4-methyl-piperidin-3-ol

To a solution of the product from Method B (72.45 grams/0.387 mol)dissolved in 240 mL of THF was added 21.4 grams of NaBH₄ and the mixturecooled to 0° C. A solution of borontrifluoride etherate (109.4 mLdissolved in 200 mL of THF) was then added dropwise over 1.5 hours. Onceadded, the reaction mixture was brought to room temperature and stirredfor 2 hours. The reaction was again cooled to 0° C. and 29.3 mL of waterwere added dropwise over 15 minutes followed by dropwise addition of 2Nsodium hydroxide (97.5 mL) over 20 minutes. The resulting mixturestirred at 0° C. for 40 minutes and was then brought to roomtemperature. Hydrogen peroxide (30%) (97.5 mL) was added dropwise at arate so as not to exceed 50° C. in the reaction mixture (approximately30 minutes). When the addition was complete, the reaction mixturestirred for 10 minutes, then was cooled to 0° C. Concentratedhydrochloric acid (97.5 mL) was added over 5 minutes, the reactionmixture was reduced to one third its volume in vacuo, and the pHadjusted to 9-10 with 6N sodium hydroxide (aq). The resulting mixturewas extracted three times with ether, the combined ether layers driedover MgSO₄ and evaporated to dryness in vacuo affording 65.32 grams(79%) of the title compound as yellow oil. LRMS: 206.1 (M+1).

Alternative Method

To a solution of the product from Method B (18.7 grams/0.1 mol) in THF(150 mL) was added NaBH₄ (6.5 grams/0.170 mol) at room temperature underN₂. The slurry was cooled to 0° C., and BF₃.OEt₂ (15 mL, 16.8grams/0.118 mol) in THF (25 mL) was slowly added through an additionfunnel. The addition was kept slow enough to keep the temperature of thereaction mixture below 0° C. After the addition; the reaction mixturewas stirred at 0° C. for 1 hour and room temperature for 1.5 hours. Thereaction was re-cooled to 0° C. and water (50 mL) was added slowly todestroy the excess borane. The reaction was stirred at room temperaturefor 2 hours, followed by the addition of Oxone® (110 grams/0.343 mol) inwater (500 mL) at 0° C. The reaction mixture was allowed to warm to roomtemperature and stirred overnight. The reaction was quenched uponaddition of solid NaHSO₃ until all excess oxidant was destroyed(Kl/starch test paper). The pH of the reaction mixture was 1-2. Thereaction mixture was then extracted 3 times with 50 mL ethyl acetate,the aqueous layer adjusted to pH 12 with 6 N sodium hydroxide andextracted with ethyl acetate (4 times with 100 mL). The organic layerwas washed with brine, dried over Na₂SO₄, and concentrated in vacuoaffording 19.0 grams (92%) of the title compound as an oil. LRMS: 206.1(M+1).

Method D

1-Benzyl-4-methyl-piperidin-3-ol-toluene-4-sulfonic Acid Salt

To a stirred solution of the product from Method C (65.32 grams/0.318mol) dissolved in 175 mL of acetone and cooled to 0° C. was added asolution of para-toluenesulfonic acid monohydrate in 350 mL of acetone(dropwise) over 2 hours and the resulting mixture stirred at 0° C. for1.5 hours. The precipitate was filtered and the filter cake washed with90 mL of diisopropyl ether. The solid product was then dried in vacuoaffording 58.55 grams (100%) of the title compound as a white solid.LRMS: 378.5 (M+1).

Method E

1-Benzyl-4-methyl-piperidin-3-one

To a solution of the product from Method D (9.8 grams/0.026 mol) and31.7 mL of diisopropylethylamine dissolved in 250 mL of dichloromethaneand cooled to 0° C. was added (dropwise) 12.4 grams of SO₃ pyridinecomplex dissolved in 153 mL of dimethylsulfoxide over a 40 minuteperiod. Once added, the reaction stirred for 1.5 hours at roomtemperature and was then quenched upon addition of 200 mL of saturatedNaHCO₃ (aq). The dichloromethane was removed in vacuo and the remainingaqueous residue extracted four times with diisopropyl ether (150 mL).The combined ether layers were washed four times with water (100 mL),dried over Na₂SO₄ and concentrated to dryness in vacuo affording 3.81grams (72.97%) of the title compound as yellow oil. LRMS: 204 (M+1).

Method F

(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-amine

To a stirred solution of the product from Method E (3.81 grams/0.019mol) and 38 mL of 2.0 M methylamine in THF was added 2.2 mL of aceticacid and the resulting mixture stirred at room temperature for 1.5hours. Triacetoxysodiumborohydride (NaB(OAc)₃H) (7.94 grams/0.038 mol)was added as a solid and the new mixture stirred at room temperature for18 hours. The reaction was quenched with 2 N hydrochloric acid and thepH adjusted to 1. The reaction mixture was washed two times with ether,the aqueous layer then adjusted to pH of 12 with 6 N sodium hydroxide(aq) and extracted three times with dichloromethane The combineddichloromethane layers were dried over Na₂SO₄, filtered and evaporatedto dryness in vacuo affording 3.51 grams (87.75%) of the title compoundas dark yellow oil. LRMS: 219.1 (M+1).

Method G

(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

A mixture of 4-chloropyrrolo[2,3-d]pyrimidine (2.4 grams, 15.9 mmol),prepared by the method of Davoll, J. Am. Chem. Soc., (1960), 82, 131,the product from Method F (1.7 grams, 7.95 mmol) and 10 mL oftriethylamine were heated in a sealed tube at 100° C. for 4 days. Aftercooling to room temperature and concentration under reduced pressure,the residue was purified by flash chromatography (silica; 3% methanol indichloromethane) affording 1.0 grams (38%) of the title compound as acolorless oil. LRMS: 336.1 (M+1).

Method H

Methyl-(4-methyl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

To the product from Method G (0.7 grams, 2.19 mmol) dissolved in 15 mLof ethanol was added 0.5 grams of 20% palladium hydroxide on carbon (50%water) (Aldrich) and the resulting mixture agitated (Parr-Shaker) underan atmosphere of hydrogen (50 psi) at room temperature for 2 days. TheCelite filtered reaction mixture was concentrated to dryness in vacuoand the residue purified by flash chromatography (silica; 5% methanol indichoromethane) affording 0.48 grams (90%) of the title compound. LRMS:246.1 (M+1).

Method I

[1-(4-Methoxy-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

To a stirred solution of 1 mL of pyridine and 9 ml of dichloromethanewas added 40 mg (0.163 mmol) of the product from Method H and 20 L of4-methoxy-benzenesulfonyl chloride and the resulting mixture stirred atroom temperature for 18 hours. The reaction was then quenched uponaddition of saturated NaHCO₃ (aq), the organic layer was removed and theaqueous layer extracted with dichloromethane. The dichloromethane layerwas dried over Na₂SO₄ and concentrated to dryness in vacuo. The residuewas purified by PTLC (silica; 10:1 dichloromethane/methanol) affording22 mg (32%) of the title compound as a light yellow solid. LRMS: 416.5(M+1).

The title compounds for examples 2-297 were prepared by a methodanalogous to that described in Example 1.

EXAMPLE 2[1-(4-Methoxy-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 416.

EXAMPLE 3(1-Benzenesulfonyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 386.

EXAMPLE 42-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-isoindole-1,3-dione

LRMS: 483.

EXAMPLE 5 Cyclohexanecarboxylic acid(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide

RMS: 463.

EXAMPLE 62-Chloro-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino]-piperidine-1-sulfonyl}-ethyl)-benzamide

LRMS: 492.

EXAMPLE 74-Chloro-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-benzamide

LRMS: 492.

EXAMPLE 8 Furan-2-carboxylic acid(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide

LRMS: 447.

EXAMPLE 93-Methoxy-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-benzamide

LRMS: 487.

EXAMPLE 10 Isoxazole-5-carboxylic acid(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide

LRMS: 448.

EXAMPLE 112,4-Difluoro-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-benzamide

LRMS: 493.

EXAMPLE 123-Chloro-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-benzamide

LRMS: 492.

EXAMPLE 133-Fluoro-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-benzamid

LRMS: 475.

EXAMPLE 142-Fluoro-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-benzamide

LRMS: 475.

EXAMPLE 154-Fluoro-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-benzamide

LRMS: 475.

EXAMPLE 16N-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-benzamide

LRMS: 457.

EXAMPLE 17 Cyclopropanecarboxylic acid(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide

LRMS: 421.

EXAMPLE 18 Cyclopentanecarboxylic acid(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide

LRMS: 449.

EXAMPLE 19Cyclopentyl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 342.

EXAMPLE 20 Tetrahydro-furan-2-carboxylic acid(2-(4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl)-ethyl)-amide

LRMS: 451.

EXAMPLE 21 Tetrahydro-furan-3-carboxylic acid(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide

LRMS: 451.

EXAMPLE 22{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-(tetrahydro-furan-2-yl)-methanone

LRMS: 344.

EXAMPLE 23{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-(tetrahvdro-furan-3-yl)-methanone

LRMS: 344.

EXAMPLE 24 Cyclohexanecarboxylic acid(3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propyl)-amide

LRMS: 427.

EXAMPLE 252-Cyclopropyl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 328.

EXAMPLE 262-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-pyrrolidine-1-carboxylicAcid Tert-Butyl Ester

LRMS: 443.

EXAMPLE 27{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-pyrrolidin-2-yl-methanone

LRMS: 343.

EXAMPLE 281-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-pyrrolidin-1-yl)-ethanoneHydrochloride

LRMS: 385.

EXAMPLE 29Furan-3-yl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 340.

EXAMPLE 30{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-pyridin-2-yl-methanone

LRMS: 351.

EXAMPLE 31{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-phenyl-methanone

LRMS: 350.

EXAMPLE 321-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-phenyl-ethanone

LRMS: 364.

EXAMPLE 332-Cyclopropyl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanoneHydrochloride

LRMS: 364.

EXAMPLE 342-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-pyrrolidine-1-carboxylicAcid Tert-Butyl Ester

LRMS: 443.

EXAMPLE 354-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid Benzylamide

LRMS: 379.

EXAMPLE 364-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid Phenylamide

LRMS: 365.

EXAMPLE 374-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid tetrahydro-furan-3-yl Ester

LRMS: 360.

EXAMPLE 381-(4-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-piperidin-1-yl)-ethanone

LRMS: 399.

EXAMPLE 392-Cyclopentyl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 356.

EXAMPLE 404-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid Cyclohexylamide

LRMS: 371.

EXAMPLE 41Azetidin-3-yl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanoneTrifluoroacetate

LRMS: 443.

EXAMPLE 42{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl-pyrrolidin-1-yl-methanone

LRMS: 343.

EXAMPLE 434-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid methyl-phenyl-amide

LRMS: 379.

EXAMPLE 44(4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-morpholin-4-yl-methanone

LRMS: 359.

EXAMPLE 45Methyl-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2′bipyridinyl-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 323.

EXAMPLE 46Methyl-(4-methyl-1-thiazol-2-yl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 329.

EXAMPLE 474-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid pyridin-3-ylamide

LRMS: 366.

EXAMPLE 484-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-fluoro-phenyl)-amide

LRMS: 383.

EXAMPLE 494-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-nitro-phenyl)-amide

LRMS: 410.

EXAMPLE 504-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-methoxy-phenyl)-amide

LRMS: 395.

EXAMPLE 514-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-benzoicAcid Ethyl Ester

LRMS: 437.

EXAMPLE 52{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-piperidin-1-yl-methanone

LRMS: 357.

EXAMPLE 53Methyl-(4-methyl-5′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 368.

EXAMPLE 544-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (3-fluoro-phenyl)-amide

LRMS: 383.

EXAMPLE 554-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAAcid (2,4-difluoro-phenyl)-amide

LRMS: 401.

EXAMPLE 56Methyl-[4-methyl-1-(pyrrolidine-1-sulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 379.

EXAMPLE 574-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (3-methoxy-phenyl)-amide

LRMS: 395.

EXAMPLE 584-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (3-nitro-phenyl)-amide

LRMS: 410.

EXAMPLE 591-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-pyrrolidine-2-carboxylicAcid Methyl Ester

LRMS: 401.

EXAMPLE 60Methyl-[4-methyl-1-(5-nitro-thiazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 374.

EXAMPLE 614-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylicAcid Methyl Ester

LRMS: 381.

EXAMPLE 62(4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-methanol

LRMS: 353.

EXAMPLE 63Methyl-[4-methyl-1-(piperidine-1-sulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino

LRMS: 393.

EXAMPLE 644-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (3-cyano-phenyl)-amide

LRMS: 390.

EXAMPLE 654-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (3,4-difluoro-phenyl)-amide

LRMS: 401.

EXAMPLE 66Methyl-[4-methyl-1-(morpholine-4-sulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 395.

EXAMPLE 674-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-chloro-phenyl)-amide

LRMS: 399.

EXAMPLE 68Methyl-[4-methyl-1-(6-methyl-pyridazin-3-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 338.

EXAMPLE 694-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-cyano-phenyl)-amide

LRMS: 390.

EXAMPLE 704-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid biphenyl-4-ylamide

LRMS:441.

EXAMPLE 714-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-trifluoromethyl-phenyl)-amide

LRMS: 433.

EXAMPLE 72Methyl-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-carbamicAcid Benzyl Ester

LRMS: 501.

EXAMPLE 73Cyclopropyl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]piperidin-1-yl}-methanone

LRMS: 314.

EXAMPLE 74Cyclobutyl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 328.

EXAMPLE 75 Tetrahydro-furan-3-carboxylic acidmethyl-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide

LRMS: 465.

EXAMPLE 76 Cyclohexanecarboxylic Acidmethyl-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide

LRMS: 477.

EXAMPLE 77(5,7-Dichloro-1H-indol-2-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 458.

EXAMPLE 784-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-benzoicAcid

LRMS: 409.

EXAMPLE 79(1-Benzooxazol-2-yl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 363.

EXAMPLE 80(1H-Indol-2-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 389.

EXAMPLE 81(5-Fluoro-1H-indol-2-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 407.

EXAMPLE 82(5-Methoxy-3-methyl-benzofuran-2-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 434.

EXAMPLE 83(5-Chloro-benzofuran-2-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 424.

EXAMPLE 84{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-(5-nitro-benzofuran-2-yl)-methanone

LRMS: 435.

EXAMPLE 85(5-Chloro-2,3-dihydro-benzofuran-2-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 426.

EXAMPLE 86(4-Hydroxy-piperidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 373.

EXAMPLE 871-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-benzofuran-5-yl)-ethanone

LRMS: 432.

EXAMPLE 881-(3-Methyl-2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-1H-indol-5-yl)-ethanone

LRMS: 445.

EXAMPLE 89[1-(5-Chloro-benzothiazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 413.

EXAMPLE 90(3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-3-aza-bicyclo[3.1.0]hex-6-yl)-carbamicAcid Tert-Butyl Ester

LRMS: 470.

EXAMPLE 913-(4-Chloro-phenoxy)-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-propan-1-one

LRMS: 428.

EXAMPLE 924-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid pyridin-2-ylamide

LRMS: 366.

EXAMPLE 931-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-piperidine-4-carboxylicAcid Amide Hydrochloride

LRMS: 436.

EXAMPLE 944-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5-chloro-pyridin-2-yl)-amide

LRMS: 400.

EXAMPLE 953-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-cyclopentanone

LRMS: 356.

EXAMPLE 96(3-Hydroxy-cyclopentyl)-{4-methyl-3-[methyl-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 358.

EXAMPLE 974-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-cyclohexanone

LRMS: 370.

EXAMPLE 983-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-cyclohexanone

LRMS: 370.

EXAMPLE 994-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5-nitro-pyridin-2-yl)-amide

LRMS: 413.

EXAMPLE 100[4-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-phenyl]-aceticAcid

LRMS: 423.

EXAMPLE 101(4-Amino-piperidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanoneHydrochloride

LRMS: 408.

EXAMPLE 1024-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (6-methyl-pyridin-2-yl)-amide

LRMS: 380.

EXAMPLE 1031-Methyl-4-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-pyrrolidin-2-one

LRMS: 371.

EXAMPLE 1041-Benzyl-3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-pyrrolidin-2-one

LRMS: 447.

EXAMPLE 1054-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5-trifluoromethyl-pyridin-2-yl)-amide

LRMS: 434.

EXAMPLE 1064-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-cyclohexanecarboxylicAcid (4-cyano-phenyl)-amide

LRMS: 389.

EXAMPLE 1074-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-carbamoyl-phenyl)-amide

LRMS: 408.

EXAMPLE 1084-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-sulfamoyl-phenyl)-amide

LRMS: 444.

EXAMPLE 1094-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5-methyl-thiazol-2-yl)-amide

LRMS: 386.

EXAMPLE 1104-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5,6-dichloro-benzothiazol-2-yl)-amide

LRMS: 491.

EXAMPLE 1114-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-methyl-thiazol-2-yl)-amide

LRMS: 386.

EXAMPLE 112Azetidin-1-yl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanoneHydrochloride

LRMS: 365.

EXAMPLE 113[2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-yl]-aceticAcid Ethyl Ester

LRMS: 458.

EXAMPLE 1144-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4,5-dimethyl-thiazol-2-yl)-amide

LRMS: 400.

EXAMPLE 115[2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-yl]-aceticAcid

LRMS: 430.

EXAMPLE 1164-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid benzothiazol-2-ylamide

LRMS: 422.

EXAMPLE 1174-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid thiazol-2-ylamide

LRMS: 372.

EXAMPLE 1184-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid [6-(2-dimethylamino-ethylamino)-pyridin-3-yl]-amide

LRMS: 452.

EXAMPLE 119N-(4-Chloro-phenyl)-2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-acetamide

LRMS: 413.

EXAMPLE 120N,N-Dimethyl-2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-acetamide

LRMS: 331.

EXAMPLE 1214-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid [6-(2-pyrrolidin-1-yl-ethylamino)-pyridin-3-yl]-amide

LRMS: 478.

EXAMPLE 122{2-[5-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-pyridin-2-yloxy]-ethyl}-carbamicAcid Tert-Butyl Ester

LRMS: 525.

EXAMPLE 1234-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid [6-(2-amino-ethoxy)-pyridin-3-yl]-amide

LRMS: 425.

EXAMPLE 1244-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-methylsulfamoyl-phenyl)-amide

LRMS: 458.

EXAMPLE 1254-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-methanesulfonyl-phenyl)-amide

LRMS: 443.

EXAMPLE 1264-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide

LRMS: 387.

EXAMPLE 1274-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-methylsulfamoyl-phenyl)-amide Hydrochloride

LRMS: 495.

EXAMPLE 128Methyl-[4-methyl-1-(1-phenyl-ethyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 350.

EXAMPLE 129(3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 359.

EXAMPLE 1304-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid Tert-Butyl Ester

LRMS: 346.

EXAMPLE 1314-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid [4-(2-dimethylamino-ethyl)-thiazol-2-yl]-amide

LRMS: 443.

EXAMPLE 1324-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid 4-methanesulfonyl-benzylamide

LRMS: 457.

EXAMPLE 1334-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (4-acetylsulfamoyl-phenyl)-amide

LRMS: 486.

EXAMPLE 1341-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-phenyl-ethane-1,2-dione

LRMS: 378.

EXAMPLE 135Methyl-[4-methyl-1-(6-methylamino-pyrimidin-4-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 353.

EXAMPLE 136Methyl-[4-methyl-1-(6-pyrrolidin-1-yl-pyrimidin-4-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 393.

EXAMPLE 137[1-(6-Benzylamino-pyrimidin-4-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 429.

EXAMPLE 138N,N-Dimethyl-N′-(6-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-pyrimidin-4-yl)-ethane-1,2-diamine

LRMS: 410.

EXAMPLE 139[1-(6-Chloro-pyrimidin-4-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 358.

EXAMPLE 140[1-(2-Fluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 354

EXAMPLE 141[1-(2-Chloro-pyrimidin-4-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 359.

EXAMPLE 142[1-(4-Chloro-pyrimidin-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 359.

EXAMPLE 143Methyl-[4-methyl-1-(2-methylamino-pyrimidin-4-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 353.

EXAMPLE 144Methyl-[4-methyl-1-(4-pyrrolidin-1-yl-pyrimidin-2-yl)-piperidin-3-yl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 353.

EXAMPLE 1454-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (3-methyl-isoxazol-5-yl)-amide

LRMS: 370.

EXAMPLE 1464-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (3-methyl-isoxazol-4-yl)-amide

LRMS: 370.

EXAMPLE 1474-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5-methyl-isoxazol-3-yl)-amide

LRMS: 370.

EXAMPLE 1484-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5-tert-butyl-isoxazol-3-yl)-amide

LRMS: 412.

EXAMPLE 1494-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid isoxazol-3-ylamide

LRMS: 356.

EXAMPLE 150N-Methyl-3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-propionamide

LRMS: 331.

EXAMPLE 1511-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-propan-2-one

LRMS: 302.

EXAMPLE 152(4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl]-oxo-aceticAcid Methyl Ester

LRMS: 332.

EXAMPLE 153(1-Cyclohexylmethyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 342.

EXAMPLE 154[1-(5-Amino-thiazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 344.

EXAMPLE 155Methyl-(4-methyl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 246.

EXAMPLE 1563-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionicAcid Methyl Ester

LRMS: 346.

EXAMPLE 157(1-Benzenesulfonylmethyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 400.

EXAMPLE 158(3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 359.

EXAMPLE 1591-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-propane-1,2-dione

LRMS: 316.

EXAMPLE 1604-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (6-sulfamoyl-pyridin-3-yl)-amide

LRMS: 445.

EXAMPLE 1614-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (6-acetylamino-pyridin-3-yl)-amide

LRMS: 423.

EXAMPLE 1624-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid [4-(2-dimethylamino-ethylsulfamoyl)-phenyl]-amide

LRMS: 515.

EXAMPLE 1634-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (6-cyano-pyridin-3-yl)-amide

LRMS: 391.

EXAMPLE 1644-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-sulfonicacid pyridin-2-ylamide

LRMS: 479.

EXAMPLE 1654-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid [6-(pyrrolidine-1-carbonyl)-pyridin-3-yl]-amide

LRMS: 463.

EXAMPLE 1662-Imidazol-1-yl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 354.

EXAMPLE 1674-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylicAcid Methylamide

LRMS: 380.

EXAMPLE 168{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl}-morpholin-4-yl-methanone

LRMS: 436.

EXAMPLE 1695-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-pyridine-2-carboxylicAcid Propylamide

LRMS: 451.

EXAMPLE 1704-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylicAcid Amide

LRMS: 366.

EXAMPLE 1714-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carbonitrile

LRMS: 348.

EXAMPLE 1724-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid [4-(pyrrolidine-1-sulfonyl)-phenyl]-amide

LRMS: 498.

EXAMPLE 1734-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid [4-(morpholine-4-sulfonyl)-phenyl]-amide

LRMS: 514.

EXAMPLE 174(3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 359.

EXAMPLE 1754-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid [6-(morpholine-4-carbonyl)-pyridin-3-yl]-amide

LRMS: 479.

EXAMPLE 1764-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid [6-(morpholine-4-carbonyl)-pyridin-3-yl]-amide

LRMS: 479.

EXAMPLE 1772-Imidazol-1-yl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 354.

EXAMPLE 1784-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid isoxazol-3-ylamide

LRMS: 356.

EXAMPLE 1794-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (2,5-dimethyl-2H-pyrazol-3-yl)-amide

LRMS: 383.

EXAMPLE 1804-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (5-cyclopropyl-2-methyl-2H-pyrazol-3-yl)-amide

LRMS: 409.

EXAMPLE 1814-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (3-methyl-isothiazol-5-yl)-amide

LRMS: 386.

EXAMPLE 1824-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzoicAcid

LRMS: 380.

EXAMPLE 183Methyl-[4-methyl-5′-(pyrrolidine-1-sulfonyl)-3,4,5,6-tetrahydro-2H-[1,2′bipyridinyl-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 456.

EXAMPLE 1844-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-sulfonicAcid Methylamide

LRMS: 416.

EXAMPLE 1854-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzenesulfonamide

LRMS: 415.

EXAMPLE 186N-tert-Butyl-4-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzenesulfonamide

LRMS: 472.

EXAMPLE 1871-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-pyrazol-1-yl-ethanone

LRMS: 354.

EXAMPLE 188Methyl-[4-methyl-1-(5-nitro-benzooxazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 408.

EXAMPLE 1894-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-sulfonicAcid (2-hydroxy-ethyl)-amide

LRMS: 446.

EXAMPLE 190N-tert-Butyl-4-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzenesulfonamide

LRMS: 471.

EXAMPLE 191N-Methyl-2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-oxo-acetamide

LRMS: 331.

EXAMPLE 192[1-(5-Ethanesulfonyl-benzooxazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 455.

EXAMPLE 193Methyl-[4-methyl-1-(5-methyl-benzooxazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 377.

EXAMPLE 1944-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (6-chloro-pyridin-3-yl)-amide

LRMS: 400.

EXAMPLE 195Methyl-(4-methyl-1-quinolin-2-yl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 373.

EXAMPLE 1964-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-sulfonicAcid Amide

LRMS: 402.

EXAMPLE 1971-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-pyrrolidin-1-yl-ethane-1,2-dione

LRMS: 371.

EXAMPLE 198Methyl-[4-methyl-1-(4-methyl-benzooxazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 377.

EXAMPLE 1991-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-morpholin-4-yl-ethane-1,2-dione

LRMS:387.

EXAMPLE 2004-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (6-methanesulfonyl-pyridin-3-yl)-amide

LRMS: 444.

EXAMPLE 2014-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (6-methanesulfonyl-pyridin-3-yl)-amide

LRMS: 444.

EXAMPLE 202Methyl-[4-methyl-1-(6-nitro-benzooxazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 408.

EXAMPLE 2034-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (6-methanesulfonyl-pyridin-3-yl)-amide

LRMS: 444.

EXAMPLE 2044-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (6-methanesulfonyl-pyridin-3-yl)-amide

LRMS: 444.

EXAMPLE 205Methyl-[4-methyl-1-(6-nitro-benzooxazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 408.

EXAMPLE 206Methyl-[4-methyl-1-(toluene-3-sulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 400.

EXAMPLE 207Methyl-[4-methyl-1-(4-trifluoromethyl-benzenesulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 454.

EXAMPLE 208(1-Benzothiazol-2-yl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 379.

EXAMPLE 209[1-(5,7-Dimethyl-benzooxazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 391.

EXAMPLE 2102-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-benzooxazole-6-carboxylicAcid Methyl Ester

LRMS: 421.

EXAMPLE 211Methyl-[4-methyl-1-(6-methyl-benzooxazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 377.

EXAMPLE 212[1-(6-Methoxy-benzooxazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 393.

EXAMPLE 213Methyl-[4-methyl-1-(5-trifluoromethyl-benzothiazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 447.

EXAMPLE 214[1-(5,7-Dichloro-benzooxazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 432.

EXAMPLE 215[1-(6-Chloro-pyridine-3-sulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 422.

EXAMPLE 216[1-(4-Chloro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 421.

EXAMPLE 217[1-(4-Fluoro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 404.

EXAMPLE 2184-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzonitrile

LRMS: 411.

EXAMPLE 2194-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzenesulfonylFluoride

LRMS: 468.

EXAMPLE 2202-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzonitrile

LRMS: 411.

EXAMPLE 2211-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-tetrazol-1-yl-ethanone

LRMS: 356.

EXAMPLE 222Methyl-[4-methyl-1-(2,2,2-trifluoro-ethanesulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 392.

EXAMPLE 223[1-(2,6-Difluoro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 422.

EXAMPLE 224[1-(4-tert-Butyl-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 442.

EXAMPLE 225[1-(2,4-Difluoro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d[pyrimidin-4-yl)-amine

LRMS: 422.

EXAMPLE 226Methyl-[4-methyl-1-(2-trifluoromethyl-benzenesulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 454.

EXAMPLE 227[1-(3,5-Bis-trifluoromethyl-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 522.

EXAMPLE 228[1-(3,5-Dichloro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 455.

EXAMPLE 2294-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzoicAcid

LRMS: 431.

EXAMPLE 230[1-(6-Chloro-pyridine-3-sulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2.3-d]pyrimidin-4-yl)-amine

LRMS: 422.

EXAMPLE 231[1-(4-Chloro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 421.

EXAMPLE 232[1-(4-Fluoro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 404.

EXAMPLE 2334-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzonitrile

LRMS: 411.

EXAMPLE 2344-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzenesulfonylFluoride

LRMS: 468.

EXAMPLE 2352-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzonitrile

LRMS: 411.

EXAMPLE 2361-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-tetrazol-1-yl-ethanone

LRMS: 356.

EXAMPLE 237Methyl-[4-methyl-1-(2,2,2-trifluoro-ethanesulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 392.

EXAMPLE 238[1-(2,6-Difluoro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 422.

EXAMPLE 2391-(4-tert-Butyl-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 442.

EXAMPLE 240[1-(2,4-Difluoro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 422.

EXAMPLE 241Methyl-[4-methyl-1-(2-trifluoromethyl-benzenesulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 454.

EXAMPLE 242[1-(3,5-Bis-trifluoromethyl-benzenesulfonyl)-4-methyl-piperidin-3-yl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 522.

EXAMPLE 243[1-(3,5-Dichloro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 455.

EXAMPLE 2444-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzoicAcid

LRMS: 431.

EXAMPLE 245(3-Fluoro-phenyl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 368.

EXAMPLE 246Isothiazol-4-yl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]primidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 357.

EXAMPLE 247{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-thiophen-3-yl-methanone

LRMS: 356.

EXAMPLE 248{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-(5-methyl-1H-pyrazol-3-yl)-methanone

LRMS: 354.

EXAMPLE 249(5-Methyl-isoxazol-3-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone.

LRMS: 355.

EXAMPLE 250{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-(5-methyl-thiophen-2-yl)-methanone

LRMS: 371.

EXAMPLE 251(4-Fluoro-phenyl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 368.

EXAMPLE 252Methyl-[4-methyl-1-(3-nitro-benzenesulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 431.

EXAMPLE 253[1-(3-Fluoro-benzenesulfonyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 404.

EXAMPLE 254(2-Fluoro-phenyl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 368.

EXAMPLE 255(1,5-Dimethyl-1H-pyrazol-3-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl]-methanone

LRMS: 368.

EXAMPLE 256(4-Methyl-3-[methyl-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-y-yl}-(2-methyl-thiazol-4-yl)-methanone

LRMS: 371.

EXAMPLE 257{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-thiazol-4-yl-methanone

LRMS: 357.

EXAMPLE 258(4-Methyl-isothiazol-5-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 371.

EXAMPLE 2592,2-Dimethyl-5-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-[1,3]dioxolan-4-one

LRMS: 403.

EXAMPLE 2602-Cyclopropyl-N-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-acetamide

LRMS: 436.

EXAMPLE 261N-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-methanesulfonamide

LRMS: 432.

EXAMPLE 262(3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 359.

EXAMPLE 2634-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzonitrile

LRMS: 362.

EXAMPLE 2643-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-benzenesulfonylFluoride

LRMS: 469.

EXAMPLE 2652,2-Dimethyl-5-(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-[1,3]dioxolan-4-one

LRMS: 402.

EXAMPLE 2664-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid Benzyl Ester

LRMS: 381.

EXAMPLE 2674-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzenesulfonamide

LRMS: 416.

EXAMPLE 268[1-(1H-imidazol-2-ylmethyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 326.

EXAMPLE 2694-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid 2-chloro-benzyl Ester

LRMS: 415.

EXAMPLE 270Methyl-[4-methyl-1-(1-methyl-1H-imidazol-2-ylmethyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 340.

EXAMPLE 2711-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-phenoxy-ethanone

LRMS: 380.

EXAMPLE 2722-(4-Fluoro-phenoxy)-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 381.

EXAMPLE 2734-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4yl)-amino]-piperidine-1-carboxylicAcid 2,2,2-trichloro-ethyl Ester

LRMS: 420.

EXAMPLE 2742-(2-Chloro-phenoxy)-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 415.

EXAMPLE 2752-(3-Chloro-phenoxy)-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 415.

EXAMPLE 2762-Methanesulfonyl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 367.

EXAMPLE 2772-(1,1-Dioxo-tetrahydro-1$I%6&-thiophen-3-yl)-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 407.

EXAMPLE 278Methyl-[4-methyl-1-(1-phenyl-ethyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 351.

EXAMPLE 2791-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-yl}-2-(toluene-4-sulfonyl)-ethanone

LRMS: 443.

EXAMPLE 2802-Hydroxy-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone

LRMS: 304.

EXAMPLE 2811-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-y)-amino]-piperidin-yl}-3-nitro-propan-1-one

LRMS: 347.

EXAMPLE 2825-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-thiazolidine-2,4-dione

LRMS: 404.

EXAMPLE 2833-Hydroxy-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-propan-1-one

LRMS: 318.

EXAMPLE 284N-(4-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-4-oxo-butyl)-methanesulfonamide

LRMS: 410.

EXAMPLE 2854-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid 2,2-dimethyl-propyl Ester

LRMS: 360.

EXAMPLE 2861-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-(thiazolidine-3-sulfonyl)-ethanone

LRMS: 440.

EXAMPLE 287(3,4-Dihydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone

LRMS: 376.

EXAMPLE 2884-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-Piperidine-1-carbonyl}-thiazolidin-2-one

LRMS: 376

EXAMPLE 2894-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid prop-2-ynyl Ester

LRMS: 328.

EXAMPLE 2904-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (2-cyano-ethyl)-amide

LRMS: 342.

EXAMPLE 2914-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (2-cyano-ethyl)-amide

LRMS: 342.

EXAMPLE 2921-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-cyclohexyl}-ethanoneOxime

LRMS: 302.

EXAMPLE 2934-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid cyanomethyl-methyl-amide

LRMS: 342.

EXAMPLE 2944-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid Isopropyl Ester

LRMS: 332.

EXAMPLE 2954-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicAcid (2-cyano-ethyl)-methyl-amide

LRMS: 356.

EXAMPLE 2964-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-pyridin-1-ol

LRMS: 355.

EXAMPLE 297{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-acetonitrile

LRMS: 285.

EXAMPLE 298[1-(2-Fluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

Method J

To a solution of the product from Method H (50 mg, mmols?) dissolved in5 mL of methanol was added 154 ul (mmols?) of 2-fluoro-benzaldehyde. Theresulting mixture stirred at room temperature for 4 hours, at whichtime, x mg (y mmol) of sodium cyanoborohydride were added and the newmixture stirred at room temperature for 18 hours. The reaction wasquenched upon addition of 2 drops of 1N NaOH (aq) and the mixtureconcentrated under reduced pressure to remove the methanol. The residuewas dissolved in chloroform and washed with water. The aqueous layer wasback washed three times with chloroform, the combined chloroformextracts dried over MgSO₄ and concentrated to dryness in vacuo. Thecrude product was then purified by flash chromatography (silica; 2.5%methanol in chloroform) affording 36 mg (47.5%) of the title compound asa white solid. LRMS: 372.4 (M+1).

The title compounds for examples 299-324 were prepared by the methodanalogous to that described in Example 298.

EXAMPLE 299(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 336.

EXAMPLE 300(1-Furan-2-ylmethyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 326.

EXAMPLE 301[1-(4-Methoxy-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 366.

EXAMPLE 302[1-(4-Fluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 354.

EXAMPLE 303Methyl-(4-methyl-1-pyridin-3-ylmethyl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 337.

EXAMPLE 304Methyl-(4-methyl-1-thiazol-2-ylmethyl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 343.

EXAMPLE 305Methyl-(4-methyl-1-pyridin-2-ylmethyl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 337.

EXAMPLE 306Methyl-[4-methyl-1-(1-phenyl-ethyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 350.

EXAMPLE 307(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 336.

EXAMPLE 308(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 336.

EXAMPLE 3093-{4-Methyl-3-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzonitrile

LRMS: 361.

EXAMPLE 310[1-(3-Fluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 354.

EXAMPLE 311[1-(3-Methoxy-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 366.

EXAMPLE 3123-{4-Methyl-3-[methyl-(7H-pVrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzoicAcid

LRMS: 380.

EXAMPLE 313[1-(2-Fluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 354.

EXAMPLE 314[1-(2,6-Difluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 372.

EXAMPLE 315Methyl-(4-methyl-1-phenethyl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 350.

EXAMPLE 3161-(2,3-Difluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 372.

EXAMPLE 317[1-(3,4-Difluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 372.

EXAMPLE 318[1-(4-Methanesulfonyl-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 414.

EXAMPLE 319Methyl-{4-methyl-1-[4-(piperidine-1-sulfonyl)-benzyl]-piperidin-3-yl}-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 483.

EXAMPLE 320[1-(3,5-Difluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 372.

EXAMPLE 321[1-(3-Chloro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 371.

EXAMPLE 322[1-(3,5-Difluoro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 372.

EXAMPLE 323[1-(3-Chloro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 371.

EXAMPLE 324[1-(3,5-Dichloro-benzyl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

LRMS: 405.

What is claimed is:
 1. A compound selected from the group consisting of:4-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzenesulfonamide;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-sulfamoyl-phenyl)-amide;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-nitro-phenyl)-amide;1-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-tetrazol-1-yl-ethanone;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-methylsulfamoyl-phenyl)-amide;(3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-methanone;[2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-yl]-aceticacid;5-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-thiazolidine-2,4-dione;{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-pipendin-1-yl}-thiazolidin-3-yl-methanone;Methyl-[4-methyl-1-(5-nitro-thiazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine;[2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]piperidine-1-carbonyl}-amino)-thiazol-4-yl]-aceticacid ethyl ester;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-methanesulfonyl-phenyl)-amide;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid thiazol-2-ylamide;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]piperidine-1-carboxylicacid (4-cyano-phenyl)-amide;{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-pyrrolidin-1-yl-methanone;Furan-2-carboxylic acid(2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide;{4-Methyl-3-{methyl-(7H-pyrrolo{2,3-d}pyrimidin-4-yl)-amino}-piperidine-1-yl}(tetrahydro-furan-3-yl)-methanone;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid isoxazol-3-ylamide;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (6-cyano-pyridin-3-yl)-amide;4-Methyl-3-[methyl-(7H-pyridin-[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (4-methyl-thiazol-2-yl)-amide;2-Cyclopropyl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone;Cyclopentyl-{4-methyl-3-{methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino}-piperidin-1-yl}-Methanone;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (3-methyl-isoxazol-4-yl)-amide;[4-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-piperidine-1-carbonyl}-amino)-phenyl]-aceticacid;[1-(5-Amino-thiazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine;4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid (3-methyl-isothiazol-5-yl)-amide;3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-cyclopentanone;and4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylicacid benzyl-methyl-amide.